Functional disorders of dopamine (DA) receptor system has been implicated in endocrine, neurological and psychiatric conditions. Detailed pharmacological evaluation and biochemical and behavioral studies of DA receptors have been made possible by the synthesis of high affinity ligands that are selective for each of the receptor subtypes. Affinity labels, drug molecules that bind specifically and irreversibly to a particular biological system, are important tools in enzyme, hormone and neurotransmitter receptor research. Affinity labeling experiments with neurotransmitter receptors have provided a wealth of information regarding the structure and biochemical and physiological function of adrenergic, cholinergic and opioid receptors. In Phase I study, we have completed the synthesis, chemical characterization and radioligand binding assays of bromoacetyl, fumaramide ester and isothiocyanate derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist) and SKF 83566 (D-1 antagonist). These novel analogs retained the high affinity and selectivity of the parent ligand for the respective receptor system. Preliminary results also indicate that these agents block DA receptors irreversibly. During the Phase II we will continue the synthesis and evaluation of affinity labels for D-1 and D-2 receptors capitalizing on the promising results from Phase I study.